Intergovernmental Relations Under the Federal-Aid Highway Program

Whenever the appearance and life of contemporary urban America is discussed, transportation receives a major share of the credit for what people cite as good and bad features of this scene. This proposition is readily accepted in the abstract by both readers and writers; having stated it, most writers on the subject attempt to give it a sense of urgency by citing some statistical measurement of a particular aspect of urban life not ordinarily thought of. Thus, in one of the first speeches which Alan Boyd made on the subject of urban transportation after his appointment as the country\u27s first Secretary of Transportation, he challenged his audience with the revelation that slightly more than 50 per cent of the total land space in Los Angeles is used for streets, highways and parking facilities. The Secretary made his point, for, at least in the mind of this listener, there was thereafter no further doubt that the construction of streets and highways and the handling of traffic thereon affected urban growth and urban life in an overriding degree

Area-Development Authorities: A New Form of Government by Proclamation

Let it be understood in the very beginning that the views of this writer regarding Public Authorities are partisan. He believes that recent years have witnessed the emergence of a new instrumentality of local government, the species of which are sometimes called port authorities, sometimes toll commissions, sometimes regional boards, but all of which are capable of being described generically as area-development authorities. He submits that these instrumentalities, while offering a unique and efficient means of performing many of the special functions which local governments in our times are called upon to undertake, have been allowed to grow away from the sound principles which must be adhered to if the form of government which our country has is to remain healthy. The writer is a partisan in that he would judge the propriety of these instrumentalities according to certain principles which should not be compromised. Specifically, he believes that power to affect vitally the public welfare inevitably carries with it the responsibility to consider the public welfare in commensurate degree

Antiplatelet therapy with aspirin, clopidogrel, and dipyridamole versus clopidogrel alone or aspirin and dipyridamole in patients with acute cerebral ischaemia (TARDIS): a randomised, open-label, phase 3 superiority trial

Background: Intensive antiplatelet therapy with three agents might be more effective than guideline treatment for preventing recurrent events in patients with acute cerebral ischaemia. We aimed to compare the safety and efficacy of intensive antiplatelet therapy (combined aspirin, clopidogrel, and dipyridamole) with that of guideline-based antiplatelet therapy. Methods: We did an international, prospective, randomised, open-label, blinded-endpoint trial in adult participants with ischaemic stroke or transient ischaemic attack (TIA) within 48 h of onset. Participants were assigned in a 1:1 ratio using computer randomisation to receive loading doses and then 30 days of intensive antiplatelet therapy (combined aspirin 75 mg, clopidogrel 75 mg, and dipyridamole 200 mg twice daily) or guideline-based therapy (comprising either clopidogrel alone or combined aspirin and dipyridamole). Randomisation was stratified by country and index event, and minimised with prognostic baseline factors, medication use, time to randomisation, stroke-related factors, and thrombolysis. The ordinal primary outcome was the combined incidence and severity of any recurrent stroke (ischaemic or haemorrhagic; assessed using the modified Rankin Scale) or TIA within 90 days, as assessed by central telephone follow-up with masking to treatment assignment, and analysed by intention to treat. This trial is registered with the ISRCTN registry, number ISRCTN47823388. Findings: 3096 participants (1556 in the intensive antiplatelet therapy group, 1540 in the guideline antiplatelet therapy group) were recruited from 106 hospitals in four countries between April 7, 2009, and March 18, 2016. The trial was stopped early on the recommendation of the data monitoring committee. The incidence and severity of recurrent stroke or TIA did not differ between intensive and guideline therapy (93 [6%] participants vs 105 [7%]; adjusted common odds ratio [cOR] 0·90, 95% CI 0·67–1·20, p=0·47). By contrast, intensive antiplatelet therapy was associated with more, and more severe, bleeding (adjusted cOR 2·54, 95% CI 2·05–3·16, p<0·0001). Interpretation: Among patients with recent cerebral ischaemia, intensive antiplatelet therapy did not reduce the incidence and severity of recurrent stroke or TIA, but did significantly increase the risk of major bleeding. Triple antiplatelet therapy should not be used in routine clinical practice

Common, low-frequency, rare, and ultra-rare coding variants contribute to COVID-19 severity

The combined impact of common and rare exonic variants in COVID-19 host genetics is currently insufficiently understood. Here, common and rare variants from whole-exome sequencing data of about 4000 SARS-CoV-2-positive individuals were used to define an interpretable machine-learning model for predicting COVID-19 severity. First, variants were converted into separate sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. The Boolean features selected by these logistic models were combined into an Integrated PolyGenic Score that offers a synthetic and interpretable index for describing the contribution of host genetics in COVID-19 severity, as demonstrated through testing in several independent cohorts. Selected features belong to ultra-rare, rare, low-frequency, and common variants, including those in linkage disequilibrium with known GWAS loci. Noteworthily, around one quarter of the selected genes are sex-specific. Pathway analysis of the selected genes associated with COVID-19 severity reflected the multi-organ nature of the disease. The proposed model might provide useful information for developing diagnostics and therapeutics, while also being able to guide bedside disease management. © 2021, The Author(s)